Hypoxic cytotoxic agents: a new approach to cancer chemotherapy

Many of the cells in solid tumors are hypoxic. This makes them resistant to killing by both radiotherapy and most commonly used anticancer drugs. The resistance towards anticancer drugs is because hypoxia induces a non-proliferative state as well as the fact that the hypoxic cells are furthest from the blood vessels in the tumor (and hence the source of drug). However, a new class of drugs - hypoxic cytotoxins can, by killing these hypoxic cells, not only overcome this resistance, but also exploit hypoxia thereby converting it into a therapeutic advantage. The first drug to be tested in the clinic purely for its activity towards hypoxic cells, tirapazamine, is described. Copyright 2000 Harcourt Publishers Ltd.